PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads ...
to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD.
Mesh Terms:
Animals, Cullin Proteins, DNA-Binding Proteins, Fatty Liver, HEK293 Cells, Hep G2 Cells, Humans, Intracellular Signaling Peptides and Proteins, Lipid Metabolism, Liver, Male, Mice, Mice, Knockout, Non-alcoholic Fatty Liver Disease, Signal Transduction, TOR Serine-Threonine Kinases
Nat Commun
Date: Dec. 24, 2020
Download Curated Data For This Publication
232317
Switch View:
  • Interactions 8